Limit test methods

In JP monographs, the specification value and testing procedure are described as a comparative limit test for the quantity of heavy metals that exist in drug substances as inorganic impurities. The permissible limit on the ppm scale for heavy metals (as Pb) is prescribed as the specification value. From the development stage to the establishment of the limit test method for a monograph, the validation in place has to be done for both the quantitative method for actual measurement and the comparative limit method with the control solution. However, the quantitative procedure has not been stated in the section on the heavy metals limit test in the JP s General Tests and other Japanese official... 

In this chapter, validation studies for developing the quantitative and JP limit test methods for heavy metals described in Specifications and Testing Methods of the drug substance section are described. Procedures to evaluate validation characteristics concerning the validation items of each test method are described. Table 7.1 summarizes the validation characteristics required by JP for testing of impurities. 

Take five or six aliquot samples from a single lot of homogeneous drug substance. The sample amount is equal to that specified in the limit test method in the Specifications and Testing Methods. ... 

The validation of heavy metals limit test method is required to evaluate the specificity and the detection limit of the limit test of impurities. However, since the JP method is capable of detecting Pb, Bi, Cu, Cd, Sn, and Hg, specificity evaluation for these metals is not required. The detection limit of the method should be evaluated visually. 

Detection Limit. The detection limit of heavy metals limit test method is obtained from the test solutions and the control solution. These solutions are prepared using one of methods 1 to 4 of the control solution preparation method. The detection limit is determined by visual inspection of a series of diluted standard lead solutions. 

Until internationally recognised and accepted test methods that accurately reflect the environmental impact of oil and oil products are available, the oil industry will be obliged to work with current, limited, test methods. The inapplicability of these methods to complex mixtures of poorly soluble compounds must be understood for the apparent failures of oil products in biodegradation tests to be placed in their correct environmental perspective. 

Microbial limit test methods should be validated by the addition of small numbers of challenge organisms in the presence of the starting material or product. 

Property Test method Units Limits Test method Units Limits... 

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